In 2011-2012 we developed orthogonal chemiluminescence screen to identify aspecifically acting inhibitors. We also designed and tested cell-based assays to monitor the effects of the inhibitors on the RanGTP and importin alpha1/importin beta-regulated nuclear import and mitotic spindle assembly. We tested those secondary screens with a group of 20 primary screen hits. Although we identified at least one validated primary screen hit that displayed activity also in the secondary screens, we are now collaborating with NCATS (formerly NCGC) to optimize the secondary screens for automated secondary screens with the entire set of 1000 candidate inhibitors. Our objective is to identify specifically acting inhibitory compounds which display the expected biological activity. This data is required to secure R03 funding for the second year of the project where we will focus on the best identified inhibitor(s) and analyze their mechanism of action and optimize their performance based on structure-activity relationship analysis.